Etomidate inhibits cell proliferation and induces apoptosis in A549 non‑small cell lung cancer cells via downregulating WWP2

Li,Deqiang; Zhang,Junlong; Yin,Lijun; Jin,Zhen; Chen,Xuejun; Meng,Xiangxue

doi:10.3892/etm.2021.10689

Etomidate inhibits cell proliferation and induces apoptosis in A549 non‑small cell lung cancer cells via downregulating WWP2

Authors:
- Deqiang Li
- Junlong Zhang
- Lijun Yin
- Zhen Jin
- Xuejun Chen
- Xiangxue Meng
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Affiliations: Department of Anesthesiology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin 301800, P.R. China, Department of Anesthesiology, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu 222000, P.R. China
Published online on: September 3, 2021 https://doi.org/10.3892/etm.2021.10689
Article Number: 1254
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Etomidate (ETO) is a commonly used intravenous anesthetic that has been reported to exert a tumor suppressive effect in several types of cancer. The present study aimed to investigate the effect of ETO on cell proliferation and apoptosis in non‑small cell lung cancer (NSCLC) cells and elucidate its potential mechanism of action. Therefore, Cell Counting Kit‑8 assay was performed to evaluate the effect of different concentrations of ETO (0, 1, 2 or 3 µg/ml) on A549 cell viability. In addition, the possible interaction between ETO and WW domain containing E3 ubiquitin protein ligase 2 (WWP2) was predicted using the STITCH database. Additionally, a stable WWP2‑overexpressing A549 cell line was constructed by transfecting A549 cells with the pcDNA3.1‑WWP2 plasmid. Cell proliferation and apoptosis were assessed using colony formation and TUNEL assays, respectively. The mRNA and protein expression levels of the apoptosis‑related proteins Bcl‑2, Bax, caspase 3 and cleaved‑caspase 3 were determined by reverse transcription‑quantitative PCR and western blotting. In addition, the expression and phosphorylation levels of proliferation‑associated genes (PCNA and Ki‑67) and proteins in the PI3K/Akt pathway were analyzed by western blotting. The results showed that treatment with ETO attenuated the cell viability and proliferation of A549 cells. ETO also promoted cell apoptosis and decreased the expression of the anti‑apoptotic protein Bcl‑2, whilst increasing that of pro‑apoptotic proteins Bax and cleaved caspase 3 in a dose‑dependent manner. Furthermore, ETO was found to negatively regulate the expression of WWP2, such that WWP2 overexpression reversed the potentiating effects of ETO on cell apoptosis. In addition, ETO promoted the expression of PTEN and reduced the phosphorylation levels of the PI3K/AKT pathway‑related proteins. These effects aforementioned could also be reversed by WWP2 overexpression. Therefore, data from the present study suggest that ETO can attenuate the progression of NSCLC through by the PI3K/AKT pathway, specifically by targeting WWP2. These findings may provide a novel target for the treatment of NSCLC.

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